In a 23‑year‑old woman with 12 kg weight loss over 5 months, intermittent dizziness, systolic hypotension (98 mm Hg), normal routine labs, low‑normal 8 am serum cortisol (6 µg/dL) and eosinophilia (~1200/µL), could this be primary adrenal insufficiency (Addison’s disease)?

Suspected Primary Adrenal Insufficiency (Addison's Disease)

Direct Recommendation

Your clinical suspicion is well‑founded: proceed immediately with a cosyntropin stimulation test to confirm primary adrenal insufficiency, and do not delay endocrinology referral. 1

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Why This Clinical Picture Strongly Suggests Addison's Disease

Your patient presents with a classic constellation for primary adrenal insufficiency:

• Significant unintentional weight loss (12 kg over 5 months) is a hallmark feature of chronic glucocorticoid and mineralocorticoid deficiency 2, 3
• Intermittent dizziness with systolic hypotension (98 mm Hg) reflects orthostatic hypotension from mineralocorticoid deficiency 2, 3
• Low‑normal 8 AM cortisol (6 µg/dL ≈ 165 nmol/L) is below the threshold that excludes adrenal insufficiency (>550 nmol/L or >18–20 µg/dL rules it out) and falls into the indeterminate zone requiring dynamic testing 1
• Eosinophilia (~1200/µL, 9%) is a recognized laboratory finding in adrenal insufficiency, though not always present 1

Critical point: A morning cortisol of 6 µg/dL is neither diagnostic nor reassuring—it sits in the gray zone where cosyntropin stimulation testing is mandatory 1.

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Diagnostic Confirmation: Cosyntropin Stimulation Test

Protocol

• Administer 0.25 mg (250 µg) cosyntropin intravenously or intramuscularly 1
• Measure serum cortisol at baseline, 30 minutes, and optionally 60 minutes post‑administration 1
• Obtain a baseline plasma ACTH before cosyntropin administration to distinguish primary from secondary adrenal insufficiency 1

Interpretation

• Peak cortisol <500 nmol/L (<18 µg/dL) at 30 or 60 minutes confirms adrenal insufficiency 1
• Peak cortisol >550 nmol/L (>18–20 µg/dL) excludes the diagnosis 1
• Markedly elevated ACTH (>300 pg/mL) with low cortisol establishes primary adrenal insufficiency without further testing 1

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Etiologic Workup After Biochemical Confirmation

First‑Line: Autoimmune Screening

• Measure 21‑hydroxylase autoantibodies—positive in ~85% of autoimmune Addison's disease in Western populations 1, 3, 4
• If positive, no further etiologic investigation is needed 1

If Autoantibodies Are Negative

• Obtain contrast‑enhanced CT scan of the adrenal glands to assess for hemorrhage, tuberculosis, metastatic disease, or infiltrative processes 1
• In males, measure very‑long‑chain fatty acids to screen for X‑linked adrenoleukodystrophy 1

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Critical Management Considerations

If the Patient Becomes Acutely Unwell

Never delay treatment for diagnostic procedures if adrenal crisis is suspected (e.g., worsening hypotension, severe vomiting, altered mental status, collapse) 1:

• Administer 100 mg IV hydrocortisone immediately 1, 5
• Infuse 0.9% saline at 1 L/hour (at least 2 L total) 1, 5
• Draw blood for cortisol and ACTH before steroid administration if feasible, but do not wait for results 1

Common Diagnostic Pitfalls to Avoid

• Do not rely on the absence of hyperkalemia to exclude primary adrenal insufficiency—it is present in only ~50% of cases 1
• Do not rely on the absence of hyperpigmentation—it develops gradually and may not yet be evident in early or subacute presentations 1
• Do not assume normal electrolytes rule out the diagnosis—10–20% of patients have normal sodium and potassium at presentation 1

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Lifelong Treatment Once Diagnosis Is Confirmed

Glucocorticoid Replacement

• Hydrocortisone 15–25 mg daily in divided doses (e.g., 10 mg at 07:00,5 mg at 12:00,2.5–5 mg at 16:00) 6, 5
• Alternative: cortisone acetate 25–37.5 mg daily or prednisone 4–5 mg daily 6, 5

Mineralocorticoid Replacement (Primary AI Only)

• Fludrocortisone 50–200 µg once daily upon awakening 6, 5
• Monitor adequacy by assessing salt cravings, orthostatic blood pressure, peripheral edema, and plasma renin activity 6, 5

Patient Education and Safety Measures

• Double or triple glucocorticoid dose during minor illness, fever, or physical stress 5
• Prescribe an emergency injectable hydrocortisone 100 mg IM kit with self‑injection training 5
• Ensure the patient wears a medical alert bracelet indicating adrenal insufficiency 5

Stress Dosing for Surgery

• Major surgery: hydrocortisone 100 mg IM before anesthesia, then 100 mg IM every 6 hours until oral intake resumes 6, 5

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Annual Monitoring and Screening for Associated Autoimmune Conditions

• Assess symptoms, weight, blood pressure, serum sodium, potassium, glucose, and HbA1c 5
• Screen thyroid function tests and vitamin B12 levels annually, as autoimmune adrenalitis frequently coexists with other autoimmune disorders 5, 3
• Screen for celiac disease (tissue transglutaminase antibodies) if the patient has episodic diarrhea 1

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Why Endocrinology Referral Is Essential

• Confirmation of the diagnosis requires specialized dynamic testing and interpretation 1
• Lifelong hormone replacement demands expert dose titration and stress‑dosing protocols 5
• Patients with newly diagnosed adrenal insufficiency require comprehensive education on crisis prevention and emergency management 5